The present invention relates to a surface active material having a new chemical composition, method for producing the same and pharmaceutical composition usable for treating hyaline-membrane disease containing the active material.
The lung of a mammal performs, as is generally known, the respiration function that imbibe atmospheric oxygen into its blood and discharge carbon-dioxide gas therefrom through the cells consisting of intra-surface of many lung alveoli (i.e., cavity portion of lung) which are connected to the trachea or airway. Virgorous investigations in recent years with respect to lung physiology, particularly to the respiratory troubles in premature infant of short gestation period, have elucidated that there is a specific material in lung alveoli that lends to the stability of the liquid-air interface therein (generally called pulmonary surfactant). The deficiency of this material causes problems in respiratory function or the so-named hyaline-membrane disease (hereinafter abbreviated HMD). Different opinions however, have been reported on the precise chemical nature, especially chemical composition, of such pulmonary surfactant which have been extracted from a living body.
For the treatment of HMD, there have hitherto been employed the so-called continuous positive airway pressure method in which air or oxygen is forced into the airway of patient through a thin pipe of polyvinyl. Another method for promoting fetal lung maturation is by administering specific steroid compounds to the mother. There also has recently been reported a method of supplementing phosphatidylcholine and phosphatidylglycerol, both of which are demonstrated as main components of the pulmonary surfactant, by instilling them into the airway [cf. Summary of Lecture Meeting of Pediatric Research Society, Atlantic City, 1970, P84; Pediatrics, 48, 547, 1971; Pediatric Research, 11, 573, 1977]. Although these conventional methods for treatment of HMD have exhibited some effect, they have not yet been regarded as producing fundamental effect.
The pulmonary surfactants extracted from the lung of mammals other than human, unavoidably contain a considerable amount of so-called foreign proteins and are contaminated generally with microorganisms, so that it is not practical to use such surfactants for the clinical treatment of human HMD.
The chemical composition of conventional pulmonary surfactants has been regarded generally as being 10-20% of protein and 80-90% lipid both based on the whole surfactant, which lipid consists of about 10% neutral lipid (e.g., triglyceride, cholesterol) and of about 90% phospholipid both based on the same, while the phosphatidylcholine content based on the total phospholipid is 86%. In this specification and claims, both "%" and "part" are on the dried matter basis unless otherwise indicated.